PROJECT SUMMARY This Shared Instrumentation Grant is being resubmitted for the purpose of upgrading our high-resolution peripheral quantitative computed tomography (HR-pQCT) scanner to the current generation XtremeCT II (XCT II), introduced in 2014. HR-pQCT scanners image peripheral anatomic sites rather than central sites, allowing dramatically increased spatial resolution compared to whole body CT scanners. The XCT II system provides the highest resolution in vivo bone imaging available on the market. The XCT I, no longer manufactured, was previously the highest-resolution system on the market. It produces 3D images of the distal extremities with voxels of 82 m (in vivo configuration) or 41 m (ex vivo configuration) with 3 minute scan times. The XCT II is capable of producing images with voxel of 61 m or 30 m, as far proximal as the distal femur, with 2 minute scan times. The XCT II provides an unparalleled combination of rapid, quantitative, high-resolution and 3D assessment of structure and density. Acquisition of the XCT II will be of tremendous benefit to our research in four main areas: 1. Osteoarthritis of the knee The ability to scan the knee at high resolution in vivo will allow our collaborators to shift from animal-model based studies to clinical human studies of OA. This will be a major paradigm shift in the study of OA pathology and progression, facilitating major breakthroughs in the understanding of OA. 2. HR-pQCT image processing and protocol development The purchase of the XCT II will allow UCSF researchers to continue developing novel image processing techniques, multi-center study protocols, and new scanner software functionality. We will continue to collaborate with Scanco Medical to incorporate these new techniques and functionality into future scanner software releases, thereby distributing them to all users of the Scanco systems. All bone imaging researchers will benefit from these developments. 3. Bone microstructure in large specimens Improved spatial resolution will enable more accurate structure assessment, and lead to more powerful outcomes from ongoing cadaver specimen studies. 4. Clinical trials Faster scan times, higher resolution, and access to the knee will positively influence our clinical imaging studies. We will produce higher quality data and therefore be able to test hypotheses with higher power and/or fewer enrolled subjects. Access to the knee will enable new clinical studies in the areas of OA, ACL injury/repair, traumatic fractures, and others currently hindered by the lack of knee imaging. 5. Pediatric imaging Improved immobilization and faster scan times have greatly improved the reliability of measurements in subjects prone to movement. Higher resolution improves accuracy in the measurement of the fine microstructure of bone during growth and development. Finally, key clinical collaborators at other institutions are using the XCT II exclusively. To be able to collaborate with these centers and to plan and lead multicenter studies, it is essential that UCSF upgrade this scanner.